Fluid flow conduits and apparatus and methods for making and joining fluid conduits

ABSTRACT

Fluid flow conduits ( 14   a,    14   b ) and apparatus ( 40 ) and methods for joining the conduits ( 14   a,    14   b ), preferably in a sterile manner, are disclosed. Each conduit ( 14, 14   b ) has a polymeric open end that is sealed by a sealing member ( 26   a,    26   b ) that may include a heating el ement ( 28 ). The polymeric end material is melted, the sealing mem bers ( 26   a,    26   b ) are moved to expose the melted open ends of the conduits ( 14   a,    14   b ) and the ends are brought together to form a fused or welded connection ( 12 ) between the conduits ( 14   a,    14   b ).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to and the benefit of U.S. PatentApplication Ser. No. 61/578,690 filed Dec. 21, 2011, U.S. PatentApplication Ser. No. 61/585,467 filed Jan. 11, 2012 and U.S. PatentApplication Ser. No. 61/617,745 filed Mar. 30, 2012, each of which ishereby incorporated by reference in its entirety.

TECHNICAL FIELD

The present disclosure relates generally to fluid flow systems and toapparatus and methods for assembling such systems. More particularly,but not exclusively, the present subject matter relates to sterile fluidflow systems, assemblies and subassemblies and to methods and apparatusfor making connections, preferably sterile connections, in such systems

BACKGROUND ART

Fluid flow systems or assemblies that are pre-sterilized and/orpre-assembled are used in a wide variety of medical and non-medicalapplications. Medical applications may include, for example,administration of medical fluids to a patient for therapeutic and/ordiagnostic purposes, blood and/or blood component or other cellcollection or processing, dialysis and other medical procedures.Non-medical applications for such systems or assemblies may include, forexample, pharmaceutical manufacturing and cell processing. In themedical field in particular, such flow systems commonly employ one ormore pre-filled containers or other sources of medical fluid or agentand an associated fluid flow circuit or system (sometimes called atubing set) containing the necessary flow tubing, valves, flowcontrollers, process chambers and the like to carry out the particularprocedure, either alone or in cooperation with a reusable controller orother device. It is not unusual, for example, for a medical fluid flowsystem to include or be used in association with a container of asuitable drug, saline, anticoagulant, dextrose solution, sterile water,cell preservative or the like, to name just a few examples.

Such a fluid flow system can, however, pose manufacturing or assemblychallenges for different reasons. One reason can be that the pre-filledcontainers of medical liquid, powder or other agent that is administeredto the patient or otherwise employed in the medical fluid flow system,require different sterilization techniques than other portions of thefluid flow system. For example, empty plastic tubing, containers, flowcontrol devices and/or processing devices or chambers, which do notcontain any substantial amount of liquid or other agent, may besterilized with gamma or electron beam (e-beam) radiation or by exposureto a sterilizing gas, e.g., ethylene oxide. However, gas sterilizationwould be ineffective to sterilize an agent, such as a liquid, powder ordrug, contained in a sealed container, and exposing the agent toionizing radiation may degrade or otherwise have a deleterious effect onthe agent. Also, there may be situations where different portions of asterile fluid flow system, even though suitable for the samesterilization process, are separately manufactured and sterilized forother reasons and then subsequently assembled in a sterile manner.

In addition sterile connections often need to be made on site, by theend user, e.g., at the location where the fluid flow systems are beingused to treat patients or collect or process blood, or blood components,or biologic materials, or in other therapeutic or diagnostic procedures.For example, it may be desired to join a fluid source, filters, tubingor the like to other apparatus without compromising the sterility of anypre-sterilized components or parts of the assembly.

As a result of these various needs, a number of different approacheshave been used in assembling sterile fluid flow systems. For example,one technique for manufacturing such systems employs the use of asterile docking system, such as a device disclosed in U.S. Pat. No.4,157,723. As illustrated there, the sterile docking system comprises apair of mating members, each having a facing membrane. One of the matingmembers is connected to a pre-sterilized container of liquid, drug orother agent and the other mating member is attached to a pre-sterilizedfluid flow system, which may include one or more empty containers. Afterthe two members are joined, the docking system is exposed to radiantenergy, causing the membranes to melt and form a sterile fluid pathwaythrough the mating members. Fluid may then be transferred from theinitial container into an empty container in the fluid flow system, andthe flow path sealed and severed. The initial container and matingmembers are then discarded. While this works satisfactorily, it entailsmultiple manufacturing steps of transferring solution from one containerto another in a sterile manner and the associated quality controlprocedures with such a step. It also requires the disposal of a portionof the product with increased product and waste cost.

Another technique for assembling medical fluid flow assemblies that havedifferent pre-sterilized portions, such as the type requiring differentsterilization processes, employs an electron beam. This technique, asdescribed in U.S. Pat. No. 5,009,645, requires a manufacturing procedureemploying an electron beam or the like to sterilize isolated portions ofsubassemblies after they have been joined together. After the isolatedregions are joined and sterilized, clamps or frangible closures whichisolate the regions may then be opened to allow for direct sterilecommunication between the subassemblies. Such a procedure and the use ofe-beam or similar radiation, of course, requires a substantialinvestment in manufacturing equipment as well as additional proceduresand safeguards during manufacture.

To avoid the use of more complicated manufacturing processes, it hasalso been disclosed to use sterilizing filters on the inlet flow linethat couples a pre-sterilized liquid container or the like to aseparately sterilized fluid flow tubing system. Such an arrangement isillustrated in U.S. Pat. No. 4,978,446. In the approach in the '446patent, however, the medical personnel are required to manually join thefluid flow tubing system to the fluid container, such as by spiking thefluid container with a piercing member associated with the fluid flowsystem. In addition to the administrative requirements for individuallyordering, storing and prescribing solutions and disposable flow systemsor sets, there is the added possibility of errors, such as by connectionof a container of an incorrect liquid or other agent or an improper flowsystem to be used in association with the procedure.

Also, there is a known device commonly referred to as sterile tubingwelder that is marketed by Terumo Medical Corporation as the “SCDDevice.” That device uses a heated wafer to slice and melt the ends oftubing, which are joined together after the wafer is removed. Aspects ofthis device are disclosed in various patents, including U.S. Pat. Nos.4,753,697, 5,158,630 and 5,156,701. Although widely used, particularlyas an “on-site” tool to allow users to assemble a system in suchconfiguration as they desire, this device requires the use of expensivewafers that are replaced after each splice.

Sterile connection systems using a melting process are found in WO2008/131442 A2 and WO 82/02528 and a sterile connection system using amovable internal wall and limited sterilization is found in U.S. Pat.No. 4,030,494.

Accordingly, there remains a significant need for advancements in thisfield.

SUMMARY

The present subject matter, as recited in part in the attachedindependent claims, is summarized below for purposes of introductiononly. This summary is not intended to be a full or complete summary orlisting of all aspects or of the broadest aspects of the present subjectmatter, and is only presented to acquaint the reader with the subjectmatter hereof, which is set forth more fully in following descriptionand in the appended claims. The subject matter of this description hasnumerous separate and independent aspects including fluid flow conduits,circuits and assemblies, individual and assembled, methods and apparatusfor making such conduits and assembling them and unique componentsemployed in such conduits and their joinder. Accordingly, the headingsused herein are only to guide the reader, and do not mean that thedescription under a particular heating is limited to or only pertains tothe specific subject matter of the heading.

In one aspect, a method is provided for joining first and second fluidflow circuits or subassemblies to form a fluid flow circuit assembly.Each fluid flow circuit or subassembly includes a fluid flow conduitwith a lumen and an open end terminating in a heat meltable material,such as a polymeric material, that softens or melts when heated andhardens upon cooling and a sealing member attached to the flow conduitand preferably sealing the open end thereof. At least one of the sealingmembers includes at least one heating element. The method includes: (a)melting the material of the open ends by heating the at least oneheating element; (b) relatively moving the sealing members and therespective open ends to which they are sealed to expose the open ends;and (c) bringing the exposed open ends together while melted to form ajunction between the fluid flow circuits that allows fluid flowtherebetween. Although the sealing member is typically referred to asclosing or sealing the fluid flow conduit, for junctions where sterilityor sterile connection is not required, the sealing member need not sealthe open end of the conduit from ambient conditions.

In another aspect, a method is provided for making a fluid flow conduitthat may be employed with other aspects of the present subject matter.The method includes providing hollow tubing having a lumen and ameltable distal end, and bonding the distal end of the tubing to asealing panel that includes a heating element or member, which sealingpanel hermetically seals the tubing. The distal end material may be apolymer or other suitable material as explained below. The panel canhave one or more layers, as in a laminated web or film for example.

In yet a further embodiment, a unique fluid flow circuit or subassemblyis provided. The fluid flow circuit includes a fluid conduit having alumen and at least one open end terminating in a heat meltable endmaterial (e.g., a polymer material) and a sealing member sealing theopen end of the conduit. The sealing member includes at least oneheating element configured to melt the end material upon energizing, andthe sealing member and open end of the conduit are relatively movable toa non-sealing position upon heating to expose the molten end material.

In another aspect, a fluid flow circuit assembly is provided comprisingfirst and second separate fluid flow circuits or subassemblies, each ofwhich includes: (i) a fluid conduit including a lumen and at least oneopen end terminating in a heat meltable end material (such as apolymeric material); (ii) a sealing member sealing the open end of theconduit; (iii) the sealing member including at least one heating elementconfigured to melt the end material upon energizing; (iv) the sealingmember being movable to a non-sealing position upon heating to exposethe molten end material; and (v) a housing carrying the sealing member.The housings of the first and second flow circuits or subassemblies areconfigured for irreversible connection to one another with the sealingmembers of each circuit being cooperatively in contact with one anotherwith the end material of each conduit being in compression, such thatupon heating of such sealing members to melt the end material of eachconduit and movement of the sealing members to expose the molten endmaterials, the molten ends engage together to form a sealed junctiontherebetween.

In a still further aspect, connection apparatus is provided for joiningtwo fluid flow circuits or subassemblies of the type comprising: a fluidconduit including a lumen and at least one open end terminating in aheat meltable end material (e.g., a polymeric material); a sealingmember sealing the open end of the conduit; the sealing member includingat least one heating element configured to melt the end material uponenergizing; and the sealing member and open end of the conduit beingrelatively movable to a non-sealing position upon heating to expose themolten end material. The connection apparatus includes: (a) opposedconduit holders, each of which is configured to hold a portion of one ofthe fluid flow circuits or subassemblies, with the open ends generallyin axial alignment. The conduit holders are relatively movable to movethe sealing members toward each other to hold them in contact with eachother. The connection apparatus also includes a power source for heatingat least one of the heating members sufficiently melt the end materialof the respective flow circuits and a sealing member holder configuredto hold the sealing members. The sealing member holder and the conduitholders are respectively laterally movable to move the sealing membersfrom between the open ends when the end material is melted.

In a still further aspect, a method of joining first and second fluidflow conduits is provided. Each of the conduits includes a lumen and anopen end terminating in a heat meltable material (e.g., polymericmaterial) and a sealing member attached to the flow conduit and sealingthe open end thereof, and each of the sealing members includes at leastone heating element. The method includes: (a) placing the sealingmembers in face to face contact; (b) melting the material of the openends by heating the at least one heating elements of each sealingmember; and (c) moving the sealing members from between the respectiveopen ends of the conduits while pressing the open ends of the conduitstoward each other to bring the exposed open ends together while meltedto form a junction between the fluid flow conduits that allows fluidflow therebetween.

DESCRIPTION OF DRAWINGS

These and other aspects are disclosed in the following detaileddescription and accompanying drawings, of which:

FIG. 1 is a plan view of an exemplary fluid flow assembly formed byjoining flow conduits of two fluid flow circuits or subassembliesemploying certain aspects of subject matter of this description.

FIG. 2 is a side view of the connection junction or union formed inaccordance with the present subject matter between two fluid conduits.

FIG. 3 is a side view of a conduit connection junction or union such asshown in FIG. 2 and in which at least one and preferably both fluidconduits include internal frangible closures to control flow.

FIGS. 4-9 are partial perspective views of two fluid conduits (which maybe part of larger fluid circuits or subassemblies), which in accordancewith the present disclosure are being connected, preferably in a sterilemanner.

FIG. 10 is a side perspective view of an exemplary apparatus that may beemployed in connecting two fluid flow conduits in accordance with thepresent subject matter.

FIG. 11 is a top perspective view of the apparatus of FIG. 10.

FIGS. 12-15 are partial top views of the apparatus of FIG. 10,illustrating sequential positions of the apparatus when connecting twofluid conduits.

FIG. 16 is a perspective view of an end portion of a fluid conduit(which may be part of a larger fluid circuit or subassembly) sealed atthe end by a sealing member in the form of a panel (which may be a webor film of one or more layers or coatings).

FIG. 17 is a perspective view of a multilayer embodiment of a sealingmember panel that has three layers.

FIG. 18 is a side view of an alternative connection assembly connectingtwo fluid conduits (which may be part of larger circuits orsubassemblies) in accordance with another aspect of the present subjectmatter.

FIG. 19 is a top view of the connection assembly of FIG. 18.

FIG. 20 is a cross-sectional view taken along lines 20-20 of FIG. 19before the conduits are connected in fluid flow relation.

FIG. 21 is an enlarged view of the connection detail in FIG. 20.

FIG. 22 is a top view of the connection assembly of FIG. 18 after thefluid flow circuits are connected in flow relation.

FIG. 23 is a cross-sectional view taken along lines 23-23 of FIG. 22.

FIG. 24 is an enlarged view of the connection detail in FIG. 23.

FIG. 25 is a side exploded view of the connection assembly of FIG. 18,also showing an induction power source mounting fixture for theassembly.

FIG. 26 is sectional view illustrating another embodiment of aconnection assembly and method for joining two fluid flow conduitsemploying certain aspects of subject matter of this description andshowing the conduits before connection.

FIG. 27 is a sectional view of the assembly of FIG. 26 in the attachedconfiguration and before the union between the conduits is formed.

DETAILED DESCRIPTION

FIG. 1 illustrates one example of a fluid circuit assembly 10, includinga connection or union 12 joining two fluid flow conduits 14 a,b, whichare illustrated as part of first and second fluid circuits orsubassemblies 16 and 18, respectively, to form the fluid circuitassembly 10. Each fluid flow circuit or subassembly 16 and 18 mayinclude additional tubing, containers, valves, separation chambers, andother selected fluid processing or storing apparatus as desired for theparticular application. As illustrated, each circuit or subassembly thefluid conduits 14 a,b of each may include one or more tubing fluid flowpaths 20 a,b and fluid containers 22 a,b, but the exact components ofeach circuit or subassembly may vary as the use requires, and fluidcontainers are optional in one or both fluid circuits.

The present subject matter has potential application in a wide varietyof environments, industries and applications. In its broader aspects, itis not limited to making sterile connections. However, it will beappreciated that it has particular application and benefit in makingsterile connections between pre-sterilized conduits, flow circuits orsubassemblies of a sterile fluid flow assembly or system, such as adisposable sterile medical fluid flow assembly. Such sterile fluid flowsystems may be found in any of a variety of medical and non-medicalapplications and systems such as (1) administration or withdrawal offluid to or from a patient for any diagnostic or therapeutic purpose,(2) collection, storage or processing of blood or blood components orother cells or cellular materials, (3) blood separating and/orcollecting systems for use with hardware such as supplied by FenwalInc., Caridian, Inc and/or Haemonetics Inc., (4) pharmaceuticalmanufacturing, (5) cell culturing and/or (6) other sterile fluid flowsystem applications where collecting, storing or processing of fluid isdesired, whether or not the system is directly attached to a human oranimal.

In one non-exclusive example, such fluid circuit assembly 10 may beconfigured for employment in the collection or processing of blood orblood components, and may comprise a preassembled, sterile, disposablemedical fluid flow system such as the type that may be associated withthe ALYX Centrifugal Blood Processing System sold by Fenwal, Inc. ofLake Zurich, Ill., and illustrated in more detail, for example, in U.S.Pat. No. 6,322,488, which is hereby incorporated by reference. The ALYXsystem is referred to only for purposes of illustration of one type of amedical fluid flow system, and the present subject matter may beemployed in any of a wide variety of sterile fluid flow systems ingeneral and disposable pre-sterilized fluid flow systems in particular.

As noted above, the present subject matter has particular application tosterile disposable medical fluid flow systems (e.g., assembly 10), thatare assembled by joining fluid circuits or circuit subassemblies (e.g.,fluid flow circuits 16 and 18) that are pre-sterilized and subsequentlyjoined together in a sterile manner to provide a sterile fluid circuitassembly of a desired configuration. This has application, for example,where the first or second fluid flow circuits are separatelypre-sterilized because one includes a therapeutic, diagnostic or otheragent that is not suitable to undergo the same sterilization process asthe other fluid flow circuit. For example, a fluid flow circuit that is“wet” (includes a sealed container of drug or other liquid) may requiresteam or heat sterilization, whereas a fluid flow circuit that is “dry”(includes only empty tubing, containers and the like) may be efficientlygas or radiation sterilized. Other factors may also dictate the type ofsterilization, such as the materials or configuration, contents orultimate use of the fluid flow circuit. In addition, the present subjectmatter has application where the first or second fluid flow circuits areseparately manufactured and pre-sterilized for reasons other thansterilization, such as convenience, manufacturing efficiency, marketing,user flexibility in assembling the desired fluid flow circuit assemblyon site and/or other reasons.

Referring back to FIG. 1, it is within the scope of this descriptionthat the first and second circuits 16 and 18 may include additionalparts or pieces of the overall system assembled in any desired way.Also, the circuits 16 and 18 may themselves be part of a larger systemor systems, the other portions of which are assembled in a differentmanner than described herein, and which are not necessarilypre-assembled in their entirety. Nor does this description preclude thepossibility that other components are subsequently attached to orassociated with circuits 16 and 18, or are added to the overall system,in a manner different than described or claimed herein.

FIG. 2 is an enlarged view of the connection or union 12 formed betweenthe fluid flow conduits 14 a,b of the respective circuit or subassembly16, 18. The connection, as described in more detail below, isspecifically a union in which the open ends of the conduits weld or fusetogether while melted to provide a permanent sealed junction between theconduits (and any associated fluid circuits or subassemblies) that isopen sufficiently to allow fluid flow therebetween. As illustrated andpreferred, the connection 12 is sufficiently strong so as not to requireany other connecting structure or reinforcement and is preferably solelya weld or fusion bond between the open conduit ends.

As described in more detail below, to achieve this welded or fusedconnection, each conduit 14 a,b terminates in an open end that is madeof a material, such as a thermoplastic polymeric material, that softenssufficiently when heated to allow the formation of a weld or fusion bondbetween the conduits and hardens when cooled. In a preferredconfiguration, the conduits each terminate in a thermoplastic polymericmaterial, preferably flexible and resilient, such as polyvinyl chloride(PVC), polypropylene (PP) or other polymeric material that becomessufficiently softened and amorphous when heated to allow the formationof a fusion bond or weld between the material at the ends of theconduits when they are brought together, and hardens when cooled. Forpurposes of this description, this softening is referred to as“melting,” and the conduit ends may be referred to as melted ormolten—although it is understood that for thermoplastic polymericmaterial this “melting” is more of the nature of a transition from acrystalline phase to an amorphous phase than an abrupt solid-liquidtransformation. References to polymeric material herein will beunderstood to refer to thermoplastic polymeric material, which exhibitsthe above properties.

Turning to FIG. 3, although the conduits 14 a,b leading to theconnection may be open for fluid flow immediately after the connection12 is made, as shown in FIG. 3 it is also contemplated the one or bothconduits may include an internal frangible closure 24 a,b. Frangibleclosures that can be opened by external manipulation, without breachingsterility, such as by manual or automated flexing or bending of theconduit tubing, are well known in the medical industry. Examples of suchfrangible closures may be found in, inter alia, U.S. Pat. Nos.4,340,049; 4,181,140 and 5,330,464 which are hereby incorporated byreference. With the frangible closures 24 a,b in one or both conduits 14a,b, the user may confirm the integrity of the connection 12, ifdesired, (for example, by performing a pull test) before allowing fluidto flow through it by opening the frangible closures.

FIGS. 4-9 diagrammatically illustrate the formation of the connection 12between the conduits 14 a,b of respective fluid flow circuits orsubassemblies 16 and 18. As noted earlier, the fluid flow circuits orsubassemblies may have any suitable configuration or components, with orwithout fluid containers. FIGS. 4-9 show only the terminal end of theconduits 14 a,b for simplicity and ease of illustration of the formationof connection or junction 12. The illustrated conduit portions may, forexample, be terminal tubing segments specifically selected forconnection as described herein, or continuation of tubing usedthroughout the respective fluid circuit or subassembly. As shown inFIGS. 4-9, each conduit has an internal lumen or bore 15 a,b defining afluid flow path. The open end of the lumen or bore of each respectiveconduit 14 a,b has attached thereto a sealing member 26 a or 26 b,respectively. The sealing member preferably closes the end of theconduit and, if the conduit is pre-sterilized, seals the conduit topreserve the sterility thereof.

Sealing Member

The sealing members 26 a,b may be of any suitable configuration, shapeor size and attached to the open end of the conduits 14 a,b by adhesive,solvent or heat weld, and may be of the same or different configurationor materials. As described in more detail below, the sealing member mayinclude at least one heating element that, during the connectionprocedure, is heated to an elevated temperature that causes the materialat the open ends of the conduits to melt. For making sterile connectionsbetween pre-sterilized fluid flow circuits or subassemblies 16 and 18the elevated temperature is preferably sufficiently high to causesterilization of the sealing members or at least those portions of thesealing members that are exposed to the sterile lumen of the conduits.

More specifically, each sealing member 26 a,b is not limited to a singleelement or device, but can be an assembly of multiple parts and piecesincluding, if desired, the heating member or element (which likewise canbe more than one part or piece). As shown in FIG. 4, the illustratedsealing members are each configured as a relatively thin panel, such asa thin web or film, that may be of a single layer or multiple layers,such as two, three or more layers or coatings or laminations. Theillustrated sealing member is a panel having two layers 28 and 30.

As depicted, layer 28 may be an electrically conductive material, suchas a conductive polymer or conductive metal, which functions as aheating member. If metallic, layer 28 may be a film or foil made singlematerial, such as copper, aluminum, stainless steel, brass, bronze, goldor silver, or an alloy thereof, or include multiple thicknesses orlayers of different metallic materials if desired. Also, metallic layer28 may have such surface treatment, coatings or addition layers for suchother purposes as may be desired, such as protection against oxidation.For purposes of this description, “film” and “foil” are usedinterchangeably. Although FIGS. 4-9 show each sealing member with twolayers, one of which is a conductive layer, it is understood that thesealing members are not required to have the identical construction,although that may be preferred from a manufacturing standpoint. Also, itis not required that each sealing member include a heating element,although that too may be preferred.

The electrically conductive material acts as a heating member, and whenenergized, such as by electrical induction, direct electrical voltageapplication, radiofrequency energy or microwave, heats to an elevatedtemperature. At present, inductive heating of the conductive material byapplying a magnetic field is preferred, in part because it does notrequire physical contact between the heating element and power source,whereas resistive heating via direct application of voltage to theconductive material is an alternative. Microwave heating also theadvantage that it does not require physical contact between the heatingelement and power source. If microwave heating is used, a coating ofsuitable material may be employed on the film or foil to betterdistribute the microwave energy.

The conductive layer 28, if a metallic conductor, preferably has athickness not substantially greater, and preferably less than or equalto about its “skin depth” for the respective electrical frequency of thecurrent-inducing voltage used. However, thicknesses greater or less thanskin depth may be used if desired for other reasons, such as ease offabricating or handling or for use with other power sources. Forexample, if the skin depth of a particular metal at the frequency of agiven electrical induction generator is so small that a metallic film ofsuch thickness is too fragile for efficient handling in a manufacturingsetting, the layer of such material may be thicker than the skin depth.Alternatively, a different metallic material and/or a different powersource frequency may be selected to optimize material usage, connectionefficiency and/or product cost.

For reference purposes only, the side or surface of the sealing element26 a, b that faces the respective terminal conduit segment 14 a,b towhich it is attached is referred to as proximal, and the side or surfacefacing away from the conduit segment is referred to as distal. Aspresently contemplated, the proximal surface of the illustratedmulti-layer panel sealing member 26 a,b, or a portion of the proximalsurface is made of or includes a layer or coating 30 of a material thatis compatible with and suitable for bonding to the respective conduit inorder to seal the open end of the conduit. For example, the sealingmember panel 26 a,b may include a PVC layer or coating that can bedirectly bonded to a PVC terminal end material of the conduit. If theend of the conduit is made of other material, such as polypropylene(PP), a proximal coating or layer of the different material (e.g., PP)may be required. It should be noted that the two layer panel of FIGS.4-8 is only exemplary, and there may be only a single layer, such as ametallic film, or there may be additional layers such as one or moreintermediate layers between the proximal layer or coating that bonds tothe conduit and the conductive layer. There may also be additionallayers or coatings proximal or distal of the conductive layer as welland/or there may be more than one conductive layer. For example, if itis desired to have a PVC or PP proximal layer for bonding to the conduit14 a,b, and the material selected for the conductive layer does not bondwell to PVC or PP, an adhesive layer may be provided between the distalconductive layer and a proximal PVC or PP layer. Layers of adhesive orother suitable material may make up one or more others layers of thesealing member, as desired. Most preferably, these materials arebiocompatible for use in medical devices and are non-toxic and do notcause toxic emissions upon heating.

Another alternative sealing member includes layer of aluminum, copper orstainless steel foil having a thickness of about 0.0005 to about 0.005inches (0.013-0.13 mm), and a PVC or other thermoplastic layer. The PVClayer may be formed by applying a PVC emulsion to the proximal surfaceof the foil. The total thickness of each laminate may be about 0.002 toabout 0.008 inches, and typically less than 0.01 inches.

As noted earlier, the sealing members are preferably relatively thin. Asa panel, which may be one or more layers, the thickness of the sealingmembers may be selected for the appropriate application. For example, apanel thickness may be less than or equal to about 0.02 inches (0.5 mm),or for making a sterile connection, as described below, the sealingmember may preferably be less than about 0.01 inches (0.25 millimeters)thick and may, for example, between about 0.002 inches (0.05 mm) andabout 0.007 inches (0.18 mm). The panel may also be thicker or thinneras desired.

Sealing Member/Conduit Attachment

As can be seen in FIGS. 4-8, the illustrated sealing members 26 a,b areeach a panel of elongated rectangular shape and preferably but notnecessarily bonded to the end of the respective conduit 14 a,b at alocation, such as an offset location, nearer to one end of the panel.This positioning leaves the remaining portion of the panel available forease of grasping, gripping or otherwise engaging, for purposes describedlater.

As described above, the material defining the open end of each conduit14 a,b is of a suitable heat meltable material, e.g., thermoplasticpolymer, such as PP or PVC. To avoid excessive melting of the end of theconduit 4, when making a sterile connection as described below, theconduit material may be preferably selected to have a melt temperatureapproaching or exceeding the sterilizing temperature. PP, for example,typically has a higher melt temperature than PVC and may be preferred incertain applications. This will be explained in greater detail below.

As shown in FIG. 4, each sealing member 26 a,b is preferablyhermetically sealed to the open end of conduit 14 a,b to seal it againstcontamination during shipping and handling, and preserve sterility ofthe conduit (and any associated fluid circuit) if it has beenpre-sterilized. Each sealing member 26 a,b is essentially as describedabove and may be of any suitable construction. In one preferredembodiment, the sealing member is in the form of a panel that includes alayer of conductive foil or film 28 that acts as a heating element, andthe proximal surface of the laminate has a layer or coating or material30 compatible with material at the conduit end. For a PP conduit endmaterial, for example, the proximal layer or coating may be PP or othercompatible material.

The sealing member 26 a,b may be hermetically sealed to the open end ofthe respective conduit 14 a,b by pressing the proximal side of the panelagainst the conduit open end and heating the foil by direct heat,induction, resistive, microwave, radiofrequency or ultrasound energy orother means until the end of the conduit and the proximal laminate layermelt sufficiently to bond or fuse together, sealing the interior offirst the fluid flow circuit 14 a,b. As explained earlier, the sealingmember may also be attached by adhesive or other means suitable for thematerials involved and the end use intended. After the sealing member isattached to the conduit, the conduit and associated fluid flow circuit16 or 18 may, if desired, be sterilized in whatever manner isappropriate for the components of the circuit, such as steam, radiation,gas or other form of sterilization. In its broader respects, the presentsubject matter is not limited to medical fluid flow assemblies or tojoining pre-sterilized fluid circuits or subassemblies. However, it isin the context of joining pre-sterilized fluid flow circuits orsubassemblies to form sterile fluid flow assemblies (for medical and/orother fluid flow applications) where the present subject matter isexpected to be particularly applicable.

As illustrated, both sealing members are multi-layer panels or laminatesof essentially the same construction, and the end material of bothconduits is preferably of the same material, such as PVC or PP, forexample. While this may be preferred, it is not required. As notedearlier, the sealing members 26 a,b may be identical or may differ. Forexample, only one sealing member may include a heating element such asconductive film or foil, as described earlier. Also, different materialsmay be used in the sealing members. It is also contemplated that theconduits may terminate in different materials and the conduits of eachsubassembly may comprise different materials at different locations. Forexample, the open end of a conduit may be of one material and theremainder formed of other materials, such as a PP for the end materialand PVC for other portions.

Forming the Connection

FIGS. 4-9 diagrammatically illustrate how the fluid flow assemblies 16and 18 are joined to form a sterile fluid flow assembly after they havebeen individually assembled and, if desired, pre-sterilized. Referringto FIG. 4, the conduits 14 a,b may each be temporarily mounted on arespective welding or bonding fixture or holder (not shown in thisfigure) with the distal end of the conduit protruding from the fixture.The welding or bonding fixtures may be of any suitable particularconfiguration or material, but are preferably configured to coaxiallyalign the open ends of conduits 14 a,b, with the distal surfaces of thesealing members 26 a,b (panels) in a face to face relation.

As illustrated in FIGS. 4 and 5, one or both of the welding fixtures areaxially movable to bring the distal surfaces of the sealing memberstogether into direct face to face contact and preferably to axiallycompress the ends of the fluid flow conduits 14 a,b together. Thecompressive force (exemplified by opposed arrows in FIG. 5) employedwill depend on the conduit materials, conduit thickness and deviceconfiguration, but it is contemplated that for conduits employing PVC orPP tubing of the size (e.g., ⅛-¼ inch OD) routinely found in disposablemedical fluid flow systems, an axial force of about 1-1.5 pounds may besufficient.

While held in contacting, face to face position, as illustrated in FIG.6, the sealing members 26 a,b are heated, such as by induction heatingof the conductive foil or film 28 as described earlier, until the foilis heated sufficiently to melt the end material of the conduits.Induction heating may be carried out by any suitable induction heaterand the metallic foil or film positioned at any suitable orientation tothe magnetic field of induction coil, although a parallel relationshipbetween the induction coil and foil (a perpendicular relationshipbetween the magnetic field and the foil) may be most preferred. Thepower of the induction heater may depend on other variables, but for aflat coil of about 2.8 inches in diameter and having 20 turns, powerfrom about 50 to 100 watts may be used at about 50 kHz and with amaximum current of about 4 A. This is but one example, however, andother electrical induction generators may be used as necessary for theparticular configuration of sealing member and conduit involved. Ifcarried out as a part of a sterile connection procedure, the elevatedtemperature is preferably high enough to sterilize the sealing members(or at least the relevant portion thereof that is exposed to theinterior of the conduit) during the limited time that heating occurs.The elevated temperature may preferably be about 230° C. or higher suchas 250-275° C., and more preferably about 260° C. or higher. Thisheating may preferably occur, for example, for about 5 or 6 seconds orless. Shorter heating times such as less than 4 seconds or 2 seconds andpotentially even less 1 second, may be preferred to reduce operatortime.

After or during heating, and while the conduit ends remain in a meltedstate, as best seen in FIGS. 7 and 8, the sealing members 26 a,b (e.g.,sealing panels) are simultaneously moved laterally from between theconduit ends. This may be done by moving either the sealing member orthe conduit holders or both. This may be done manually or automatically.In the illustrated example, the conduits are held stationary and thesealing members pulled from between them. As the sealing members arepulled from between the ends of the conduits, the axial compressiveforce of the welding fixtures or conduit holders simultaneously andprogressively forces the molten open ends of the conduits together in aface to face abutting relationship, and the molten ends of the conduitsweld or fuse together. This preferably happens relatively quickly, suchas 1-2 seconds or less.

In this illustration, the portion of the sealing member panel film orfoil 28 that moves or slides over the open end of each conduit 14 a,b isexposed to the environment inside the conduit. If the respective fluidsubassembly is pre-sterilized, that portion of the sealing member isexposed to the sterile field inside the conduit. To preventcontamination, the earlier heating of the sealing member preferablyraises the temperature sufficiently high not only to cause melting ofthe distal end of the conduit 14 a,b, but also to sterilize the surfacesof the sealing member that are exposed to the sterile field inside thefluid circuit as the panel is pulled or dragged across the end of thetubing segment. This could be all the surfaces of the sealing member orjust those surfaces, such as the metallic layer surfaces, that areexposed to the inside lumen or bore 15 a,b of the conduit 14 a,b. Thus,these surfaces do not contaminate the inside of the conduit, and thesterility of the conduit and any associated fluid circuit is maintainedas the panel is pulled away from its original sealed position in orderto expose the melted end of the conduit for contact with the opposedconduit. This happens simultaneously with each sealing member 26 a,b ofeach subassembly 16 and 18, and the ends of the conduits 14 a,bimmediately engage and seal together as the sealing members arewithdrawn, without contamination from the ambient environment—so thesterility of each fluid circuit is maintained.

After the sealing members are removed, the ends of the conduits are heldtogether in compression by the holders while the connection is allowedto cool and the end material to harden. This requires only a short time,such as a matter of seconds for polymeric material. Fewer than 10seconds, and even less, such as 7 seconds or less, may allow forsufficient cooling of PVC or PP conduit end material. As a result, thefluid flow assemblies 16 and 18 are joined in sterile manner with apermanent welded or fused junction or union 12, as seen in isolated viewin FIG. 9. The flow circuit conduits may then be removed from thewelding fixtures or holders and the resulting assembly or product isreading for use without further manipulation of the junction (asrequired in some prior art wafer systems), or for such furthermanufacturing steps as may be desired.

Connection Device

FIGS. 10-15 illustrate one version of a device or apparatus generally at40 for carrying out the method described for making a connection,preferably in a sterile manner, between fluid flow conduits 14 orsimilar tubing of flow circuits or fluid flow subassemblies. In brief,the apparatus 40 includes two conduit holders 42 a,b, power source 44(seen in FIG. 10) and sealing member holder or puller 46, the operationof which may be automatically controlled by a controller employing, forexample, a programmable microprocessor that is programmed to carry outthe sequence of operations described below, or any appropriate part ofthem.

The illustrated tube holders 42 a,b, are each configured to clamp orgrip a conduit 14 a,b for movement toward and away from each other. Asshown, each tube holder has a base 48 and clamp arm or jaw 50 pivotallymounted to the base and pivotal between a raised loading position, asshown in FIGS. 10 and 11 to allow positioning or insertion of conduits14 a,b into position for connection and a lowered clamping position(FIGS. 12-15) the conduit is clamped between the base and upper jaw.

Although the details may vary, in the embodiment illustrated, the baseis configured with a jaw surface that includes an elongated slot orgroove 52 for receiving a conduit 14 a,b. The upper jaw or clamp arm 50has a similar slot or groove 54. The slots or grooves 52 and 54 are inalignment or registration when the upper jaw is in the lower clampingposition and are sized to annularly grip the conduit.

The tube/conduit holders 42 a,b are relatively movable. As illustrated,conduit holder 42 b is stationary and conduit holder 42 a is mounted forlinear movement along track 56, but both could be movable if desired.Tube holder 42 a may be automatically or manually moved by any suitableapparatus, such as mechanical, electrical, hydraulic or pneumatic, forexample a solenoid, stepper motor, gear drive, piston or otherarrangement.

In any event, the tube holders 42 a and 42 b are preferably relativelymovable between a first spaced apart position or station, where theconduits are loaded into the respective holders (see FIGS. 11 and 12),and a second more closely spaced connecting position or station (seeFIGS. 13-15) where the connection is made. As seen in FIGS. 11-15 theconduit/tube holders 42 a and 42 b are positioned so that the conduitsare held in axial alignment along center axis 58 and are relativelylinearly movable toward and away from one another along that axis sothat the conduits are maintained in axial alignment to achieve theeventual fusion connection.

FIG. 11 depicts the pair conduits 14 a,b with attached sealing members26 a,b, being moved into position for loading into receiving slot orgroove 52 in the respective conduit holder 42 a and 42 b. As describedearlier, the illustrated conduits 14 a,b may each be part of a largerfluid flow circuit or flow subassembly 16 or 18, as shown for exemplarypurposes in FIG. 1, which are not shown in FIGS. 11-16 for purposes ofsimplicity and description only.

In the illustrated embodiment described earlier, each conduit 14 a,b isattached to respective sealing member 26 a,b in an off-set position.This allows a portion of the sealing member, such as a portion of thepanel, to extend sufficiently laterally for gripping or holding. In theillustrated device 40, the sealing member holder or puller 46 isprovided for grasping or gripping the sealing members. While such asealing member holder 46 may take various configurations, in theillustrated device, the holder as illustrated is mounted laterally ofthe conduit holders at the connecting or sealing station.

The conduits holders 42 a,b and sealing member holder 46 are relativelymovable and, as shown, the conduit holders are laterally stationary andthe sealing member holder is movable between a first position laterallyspaced from the conduit holders (FIGS. 10-12, 15) and a second positioncloser to the conduit holders for grasping or gripping the sealingmembers (FIGS. 13-14). The sealing member holder may be moved by anysuitable means, mechanically, electronically, hydraulically,pneumatically, or manually such as solenoid, gear arrangement, piston,stepper motor or other.

As seen in more detail in FIGS. 10, and 12-15, the illustrated sealingmember holder 46 has a pair of laterally extending pinchers or gripperarms or fingers 60. The pinchers are controlled, for example by anysuitable mechanism (electrical, mechanical, hydraulic or pneumatic) ormanually for operation between open spaced apart position (see, e.g.,FIG. 12) and a closed pinching or gripping position (see, e.g., FIG. 13)for grasping the sealing members. As described earlier and below,relative lateral movement between the conduit holders 42 a,b and thesealing member holder 46 moves the sealing members 26 a,b from betweenthe conduits 14 a,b when the ends of the conduit are melted.

For heating the sealing members and melting the ends of conduits 14 a,b,the device 40 also includes the power source 44 (FIG. 10). The powersource may take the form or any suitable energy source, such as anelectrical induction generator, direct voltage source, microwavegenerator, or other. In the illustrated embodiment, the heating elementof the sealing member or members is heated by induction heating byinducing eddy currents in the heating element(s) by magnetic fieldgenerated by an induction generator. As illustrated, the eddy currentsare induced in the heating element by a magnetic field generated by theflow of electricity in coils 62. Coils 62 are preferrably positioned togenerate lines of magnetic flux that intersect the heating element in asealing member (e.g., flux lines perpendicular to a metallic film orlayer 28 in the sealing member) to generate a current flow within theheating element that causes it to heat. As shown, the coils 62 areoffset to one side of the sealing station. If the sealing station werelocated within the coils themselves, the power requirement for theinduction generator could be considerably less. In the illustratedembodiment, one power source may be a 2.4 kW generator operated at about200-300 A at about 200 KHz, such the Ameritherm EasyHeat 0224, fromAmeritherm Inc. of Scottsville, N.Y.

The power source may employ any suitable electrical generator forcreating eddy current flow within the heating element, but it may bepreferred for the frequency of the current flow within the coils to beapproximately matched to the thickness of the heating element. Forexample, as mentioned earlier, much of the induced electrical current ina conductor occurs within a limited thickness near the surface of theconductor, referred to as “one skin depth”. The skin depth for a givenmaterial varies with the frequency of the inducing magnetic field. Asexamples, for an induction field having a frequency of about 200 KHZ,the thickness of one skin depth is about 14.6 μm (0.00057 inches) forcopper and about 18.9 μm (0.00074 inches) for aluminum. Thus, havingheating elements that are of particularly large thickness relative tothe skin depth may be unnecessary and of diminishing effectiveness forinduction heating, at a given frequency. In the present disclosure aheating element, such as a metallic layer or film, may be equal to orless than the skin depth. However, if such results in a metal layer thatis too thin or fragile or otherwise unsuited for manufacturing orproduction purposes, the metallic layer may be of such thickness as ispractical in those circumstances.

Use of Connection Device

Turning now to the method of making a sterile connection employingapparatus as shown in 10-15. FIG. 10 illustrates the device before anyloading steps are taken. The conduit holder 42 a and 42 b are spacedapart in loading position and the sealing member holder 46 is spacedfrom the conduit holders.

FIG. 11 shows the conduits 14 a,b being positioned into the conduitholders 42 a,b, with the sealing members 26 a,b in face-to-facerelation. In this illustration, the sealing members 26 a,b are in theform of relative thin panels such as webs or films, preferably amulti-layer panel, with one layer of at least one of the sealing membersbeing a conductive metallic layer or foil that acts as a heatingelement.

FIG. 12, taken from above, shows the conduits 14 a,b held in place inthe conduit holders 42 a and 42 b, with the clamp jaws 50 lowered, andthe holders still spaced apart in the loading position.

FIG. 13, shows tube holder 42 a moved toward tube holder 42 b, bringingthe sealing members 26 a,b together with the distal surfaces in face toface contact and exerting an axial compressive force on ends of theconduits 14 a,b. In this figure, the sealing member holder 46 has movedinto closer position, with a portion of the sealing members locatedbetween the grippers 60, which are shown in a pinching position. Thedashed lines represent magnetic flux generated by coils 62 of the powersource 44 to induce current in the heating member in at least onesealing member. The heating continues for a time sufficient to melt theopen ends of both conduits 14 a,b and preferably to sterilize thesealing members, or at least those portions of the sealing members thatare exposed to the interior of the conduits when the sealing members aremoved from between the conduit ends. Thus, if the conduits arepre-sterilized the sterile field therewithin will not be contaminated bypathogens from the sealing members.

The time and temperature of such heating will vary, depending on thematerials selected, the magnetic flux and whether a sterile procedure isdesired. For efficiency, it is contemplated that the heating may requirea relatively short heating time. In a sterile connection situation thesealing members are preferably heated to a sterilization temperaturesuch as at least 230° C. and preferably about 250-275° C., and at least260° C. for about 2-5 seconds. It may be noted as this point that for asterile connection, it is preferred that the material defining the openconnection ends of the conduits have a melt point equal to or higherthan the sterilizing temperature to better confirm sterility before theconduits are melted to form the junction or union 12.

After the polymeric ends of the conduits 14 a,b has melted sufficiently,and before cooling, the sealing member holder 46 is moved laterally,pulling the sealing member panels 26 a,b from between the conduits 14a,b. This action occurs relatively quickly, such as less than 1 or 2seconds. The axial pressure exerted by the conduit holders 42 a,bsimultaneous presses the open ends of the conduits progressivelytogether as the sealing members are pulled from between them, preventingambient contamination of the inside of the conduits. The conduit holderscontinue to press the ends of the conduits together during cooling, anduntil the ends of the conduit fuse together and harden in a permanentfusion or welded junction 12. The time for cooling can vary depending onthe conduit end material and temperature, and preferably is not longerthan 5-10 seconds.

After cooling, the clamp arms 50 of conduit holders 42 a and 42 b areopened and the sealed conduits 14 a,b may be removed from the holders,with a permanent connection or union 12 formed between them that allowsfluid flow between the conduits without further user manipulation orprocessing.

Alternative Sealing Member/Conduit

FIGS. 16 and 17 illustrate an embodiment of conduit 14 a,b and sealingmember 26 a,b, that is presently contemplated as one possibly preferredconfiguration for sterile connection applications. As shown there,conduit 14 a,b is a hollow tubular structure with an interior lumen orbore 15 a,b and is made of a polypropylene (PP) material or othersuitable material, which has a melt temperature preferably at or abovesterilization temperature, which helps assure that sterilizationtemperatures have been reached and/or exceeded when the conduit ismelted. The size of the tubing may vary as needed for the particularapplication. The illustrated sample has an inner diameter of about 4.1mm and an outer diameter of about 6 mm.

The illustrated sealing member 26 a,b is a triple-layer panel or webhaving outer layers of polymer, and a middle layer of electricallyconductive metal or conductive polymer. More specifically, the proximallayer is of a material that is compatible with the material at the openend of the conduit, such PP and is preferably melt bondable to PP—forexample for bonding to an open terminal end of conduit 14 a,b in FIG.16. As shown, this layer 64 is PP and, although thickness may vary, isillustrated with a thickness of about 0.05 mm. The distal polymer layer66, is polyethylene terephthalate, and has a thickness of about 0.013mm. The middle layer 68 is preferably metallic, electrically conductiveand may be made of any of the materials identified earlier or alloys,and preferably a material exhibiting antimicrobial properties, asdiscussed in more detail later. The illustrated middle layer is analuminum foil having a thickness of about 0.05 mm. The sealing member 26a,b of FIG. 17 is heat bonded to the open end of conduit 14 a,b bydirect heat weld of the PP layer to the PP conduit to hermetically sealthe open end of the conduit.

It is noted that many medical fluid flow systems use PVC tubing. If PPis used as the material at the end of the fluid flow conduit 14 a,b, itmay be necessary to provide a connection transition member or otherarrangement between the PP conduit and PVC tubing due to certainmaterial incompatibilities between PVC and PP. Such a transition membermay take any suitable configuration without departing from the presentdisclosure.

The conduit/sealing member assembly of FIGS. 16 and 17 is believed to beof particular use in providing sterile connections using the method andapparatus described earlier. Specifically, when the heating element(middle layer 68) of the sealing member is heated to at least about 230°C., such as 250-275° C. and preferably at least about 260° C. for atleast 2 seconds and preferably at least 3 or 4 seconds, sterileconnections can be formed between molten PP conduit end material. Aftercooling, the conduit is immediately ready for fluid flow without theneed to manipulate the junction or union 12, as is required for othersystems.

Alternative Embodiment

FIG. 18 illustrates one example of a fluid circuit assembly 70,including a connection assembly 72 joining two fluid flow circuits orsubassemblies 74 and 76 to form the fluid circuit assembly 70. Eachfluid circuit or subassembly 74 and 76 may include additional tubing,containers, valves, separation chambers, and other selected fluidprocessing or storing apparatus, not shown, as desired for a particularapplication or end use. In its broader aspects, this embodiment is notlimited to making sterile connections. However, it will be appreciatedthat it has particular application and benefit in making sterileconnections between pre-sterilized components, flow circuits orsubassemblies of a sterile fluid flow assembly or system, such as adisposable sterile medical fluid flow assembly.

More specifically, FIG. 18 illustrates a fluid circuit assembly in theform of a disposable flow system 70 which comprises at least two flowcircuits or subassemblies that may be pre-sterilized and, morespecifically, at least a first fluid flow circuit 74 and a second fluidflow circuit 76. As noted above, it is within the scope of thisdescription that the first and second circuits 74 and 76 may includeadditional parts or pieces of the overall system assembled in anydesired way.

Turning to FIG. 20, which is inverted relative to FIG. 18, the portionof the first fluid circuit or subassembly 74 shown in the drawingsincludes tubing 78, housing 80, terminal tubing segment 82 and a sealingmember 84. The tubing and tubing segment are hollow for the flow ofliquid therethrough, and may be formed of any suitable material such asa flexible resilient material, such as PP or PVC or other thermoplasticmaterial or other plastic that also preferably lends itself to bondingto the housing and/or sealing member, such as by melt or fusion oradhesive bonding. The tubing 78 and tubing segment 82 need not be of thesame material, but it is generally preferred for reasons evident laterthat at least the tubing segment be pliable and resilient.

The housing 80 may be of any suitable configuration or shape. As shownfor purposes of illustration only, the housing is made of rigidmaterial, such as rigid plastic for disposability and tubing bondingpurposes. The illustrated housing is generally oval with a flat wall 86and depending side wall 88 that together define an internal recessedarea or volume, which may be temporarily sealed or protected by aremovable cover (not shown), such as a dust cover sealed to the loweredge of the side wall. For fluid flow therethrough, the housing has agenerally L-shaped fluid passageway 90 with an inlet for attachment oftubing 78 and an outlet within the recessed area for attaching theterminal tubing segment 82. Together, the tubing, housing and tubingsegment form a fluid flow conduit of the first circuit 74 that, asexplained in more detail below, is to be attached, preferably in asterile manner, to a fluid flow conduit of the second fluid flow circuit76.

Turning now to the sealing member 84, “sealing member” is, as describedearlier, not limited to a single element or layer, but can be anassembly of multiple parts and pieces, including a heating member orelement (which likewise can be more than one part or piece).

For reference purposes only, the side of the sealing element or panel 84that faces the terminal tubing segment 82 to which it is attached isreferred to as proximal, and the side or surface facing away from thetubing segment is referred to as distal. As presently contemplated, theproximal surface of the panel 84 or a portion of the proximal surfaceincludes a layer or coating of a material that is compatible with andsuitable for bonding to the terminal tubing segment 82 in order to sealthe open end of the tubing segment. For example, the panel may include aPP or PVC layer or coating that can be directly bonded to PP or PVC ofthe tubing segment. If the tubing segment 82 is made of other material,a coating or layer of different material may be required. There may alsobe one or more intermediate layers between the proximal layer or coatingthat bonds to the tubing segment and the conductive layer, and/or theremay be additional layers or coatings distal of the conductive layer aswell. In general, the earlier description of the sealing member isequally applicable here, and will not be repeated in its entirety.

The illustrated sealing member (e.g., panel 84) is of elongated ovalshape and bonded to the terminal tubing segment 82 near one end of thepanel. The remaining portion of the panel extends from the terminaltubing segment into the recessed area of the housing 80. As explained inmore detail below and shown in FIGS. 19, 20, 22 and 23, the housingincludes an elongated access port 92 that allows access to the panel byan actuating member for moving the panel, after or during heating butpreferably while the foil is still hot and the plastic tube segment endis molten, from a sealed and closed position (FIGS. 19, 20 and 21)covering the open end of the terminal tubing segment, to a non-sealing,open position (FIGS. 22, 23 and 24), separated from the tubing segmentand exposing the open end of the tubing segment. For cooperation withsuch an actuating member, the panel may include an aperture 85 alignedwith the access port to allow insertion of the actuating member fingeror pin through the port and into the aperture.

The illustrated fluid conduit of the second fluid flow circuit 76 isconstructed generally similarly to that of the first flow circuit 74described above, and includes tubing 96, housing 98, terminal tubingsegment 100 and sealing member 102 in the form of a panel (e.g., alaminated film or web) bonded or otherwise sealably attached to the openend of the tubing segment 100 to seal it closed. The housing 98 has aninternal L-shaped flow path 104 with an inlet port for attachment totubing 96 and an outlet port for attachment to the terminal tubingsegment 100.

The sealing member (panel) 102 as shown is essentially the same as thesealing member 84 of the first fluid flow circuit, although they maydiffer, and only one may contain a heating member or element if desired.The sealing member or panel 102 is attached to the terminal tubingsegment 100 in the same manner as described with respect to flow circuit74.

The housing 98 of the second fluid flow circuit 76 may be of anysuitable configuration, but in the illustrated embodiment is of rigidplastic material and configured for attachment to the housing 80 of thefirst fluid flow circuit—preferably an irreversible attachment.“Irreversible attachment” means attachment in a manner that preventsseparation in the normal course of usage and handling, and maintainsattachment except upon application of unusually large and potentiallydestructive forces or manipulation not normally encountered in routineuse. The housing 98 is generally oval and has a flat upper wall 106 anda depending side wall 108 that defines a recessed area or regiontherewithin, which can be covered by a closure or dust cover, not shown.The housing 98 is sized so that it is slightly smaller than housing 80and can be inserted into housing 80. For irreversible attachment thehousings 80 and 98 have interfering surfaces that engage to preventseparation as described above. Specifically, as shown for illustrativepurposes only, side wall of housing 98 has opposed flexible fingers 110with end hooks or flanges 112 that snap or otherwise fit into receivingapertures or slots 114 in the housing 80 to prevent separation in normalusage.

As best shown in FIGS. 18-20, the housings 80 and 98 are configured anddimensioned so that when attached, the distal surfaces of the sealingmembers or panels 84 and 102 are pressed into direct face to facecontact. Also, the resilient terminal tubing segments 82 and 100 arelocated in opposed coaxial registration with one another, with at leastone of the tubing segments and preferably both being compressedsufficiently that when the sealing members are removed from betweenthem, the tubing segment(s) expand into direct end-to-end contact. Thisface to face positioning of the sealing members also allows an actuatingmember to extend through housing access port 92 and the apertures 94 inboth sealing members so as to move both sealing members 84 and 102simultaneously upon heating and melting of terminal end segments 82 and100.

As noted above, preferably the tubing segment or segments 82 and 100 arecompressed sufficiently so that when the sealing members or panels 84and 102 are heated (as by induction, microwave, direct voltageapplication or other) to sterilizing temperature and the tubing segmentsdistal ends melted, and the sealing members are pulled laterally frombetween the segments, the segment(s) expand from the compressed positionand the molten open ends of the tubing segments press togetherprogressively under pressure from the inherent resiliency of the tubingsegment material and fuse or weld together to form a generally permanentjunction or union between the flow paths of the two fluid flow circuits(see FIG. 24). This is carried out relatively quickly and the junctionor union is formed without exposure of the inside of the sterile fluidcircuits to ambient atmosphere that would render them non-sterile,thereby providing, in preferred form, a novel and highly functional andefficient sterile connection device and method suitable for joiningpre-sterilized fluid circuits or subassemblies to create sterileassemblies thereof. As can be seen in these figures, the sealing membersare enclosed in their respective housings prior to attachment of thehousings together and are enclosed within the attached housings both inthe closed position (FIG. 20) and in the open position (FIG. 23), whichreduces waste handling and simplifies functionality.

FIG. 25 illustrates the housing connection assembly 70 in combinationwith a mounting or receiving fixture 116. Fixture 116 may be of anydesired configuration and/or associated with any desired apparatus orpiece of equipment. The fixture 116 has a slotted receiving station orrecess that generally corresponds to the shape of the assembled housing.The fixture may be attached to another apparatus, such as a bloodprocessing centrifuge used by blood banks and the like (e.g., the FenwalAlyx or Amicus systems) or may be part of a sealing apparatus that isdevoted to making sterile sealed junctions between fluid processingcomponents (as in the Terumo SCD Device) or may be part of amanufacturing system for use in more basic manufacturing processes thatassemble systems for subsequent consumer usage. In any event, it iscontemplated that the fixture 116 has an electrical induction coil ormicrowave antenna built into it or into other apparatus in closeproximity to it, for induction or microwave heating of the sealingmembers 84, 102. If resistive heating is employed via direct voltagecontacts, the fixture could have voltage contact points that are wiredvia the housing to the heating element in one or both of the sealingmembers.

In addition, the fixture or associated apparatus could include anactuating member that extends through access port 92 of the housing toprovide automated movement of the sealing member panels (laminates) fromthe closed position shown in FIG. 20 to the open position shown in FIG.23, although it should be noted that manual actuation is also possible.If part of an automated operation, the fixture and/or related apparatuscould include a timer, temperature sensor and any associated controlcircuitry or programmable processor for actuating the heating of thesealing members and moving the sealing members to expose the open endsof the flow circuit (the open ends of the tubing segments) and form thesterile union between the circuits.

Assembly Method of Alternative

The method of making the fluid flow circuit assembly 70, preferably bysterile connection of two pre-sterilized fluid flow circuits orsubassemblies, is one of the particularly beneficial aspects of thepresent subject matter. The method may be used in any suitableenvironment, such as in a manufacturing facility in the course ofmanufacturing a product for commercial sale, on-site to allow thecustomer or user to join product components in such a configuration asdesired, or for other purposes. The resulting flow circuit assembly maybe for medical fluids, including blood, intravenous solutions such assaline or dextrose, sterile water, anticoagulants, blood componentpreservatives, or any other desired fluid. In broader respect, the fluidcould even be a gas.

Referring to the drawings, which represent one example of how such fluidflow circuits may be joined, the fluid flow circuit assembly 70 ispreferably formed by sterile attachment of the pre-sterilized fluid flowcircuits or subassemblies 74 and 76, which may require differentsterilization or production processes as described earlier or which maybe separately produced and sterilized for other reasons. As describedabove, the pre-sterilized flow circuits 74 and 76 each include a flowconduit in the form of tubing 78, 96, a housing flow path 90, 104 andterminal tubing segment 82, 100. The terminal ends of the flow conduits,i.e., the material of the terminal end segments, are of a heat meltablematerial, such as PP, PVC or other thermoplastic polymeric material.Each circuit or subassembly also includes a sealing member 84, 102,shown in the form of a thin panel, such as a multi-layer web or filmthat is attached to the terminal end tube segment and seals the open endof the respective flow conduit. In the illustrated example, the sealingmember is hermetically sealed to the end segment to maintain the insideof the respective fluid circuit sterile. At least one and preferablyboth of the sealing members include a heating element, such as ametallic foil or film described earlier.

To join the fluid flow circuits in a sterile manner, any dust cover isremoved from the housing housings 80 and 98, and the housings areirreversibly attached, such as by inserting housing 98 into housing 80until the side hooks 112 snap into slots or apertures 114. In thisposition, the distal surfaces of the sealing members (e.g., the distalsurfaces of the panels) are in direct face-to-face contact, as seen inFIGS. 20 and 23, and one or preferably both of the tubing end segments82, 100 are compressed.

The assembled housing or connection assembly 72 may then inserted intothe receiving slot of fixture 116. Preferably each sealing member isthen heated by an energy source such as an induction coil positioned tocreate a magnetic field that causes induction heating in the heatingelement or elements. The induction coil is preferably energized with asuitable alternating current for a time sufficient to heat the heatingelement film or foil to a sterilizing temperature, which also serves tomelt the ends of the tubing segments 82, 100. The conductive film orfoil is preferably raised to a temperature sufficient to sterilize atleast the surfaces of the laminates and/or film or foil that may beexposed to the sterile field within each of the fluid flow circuits, andspecifically the foil or film is preferably heated to at least about230° C. and preferably 250-275° C. and more preferably at least about260° C. Depending on the power of the induction heating coil or otherenergy source and location relative to the heating member film or foil,it is anticipated that less than 10 seconds and preferably less than 5seconds will be needed to raise the temperature to sterilize the desiredsurfaces. Because it occurs so quickly, this may be referred to a “flashheating.” At such temperature, it is understood that only limited time,e.g., less than a few seconds and preferably less than a second (or onthat order of magnitude), is required to sterilize the surfaces of thepanel and/or film or foil. If only one sealing member has a heatingelement, that element will also serve to heat and sterilize the othersealing element.

As the heating element(s) are heated to preferably sterilize thesurfaces of the sealing members, the material of the terminal endsegments 82, 100 of each fluid circuit is also simultaneously heated.More specifically, the terminal end segments are heated by the heatingelement beyond their melt temperature, causing melting of at least atthe terminal end edges of the tube segments. If the segments are made ofPVC, such melting will typically occur at about 176° C. or above. Ifhigher temperatures are desired for better assurance of sterilization,other materials may be selected for the terminal end segments of thefluid flow paths—such as polypropylene.

After the surfaces of the sealing members/foil or film are sterile, ifdesired, and the terminal end segments melted, the sealing members 84,102 are simultaneously moved or pulled laterally from between the facingend segments. In an automated system, this could be done relativelyquickly and smoothly by a movable pin or finger that extends through theaccess port or slot 92 and into aligned apertures 94 in each sealingmember. The pin or finger movement could be automatically controlled bya solenoid or other such device, or it could be done manually ifdesired. As noted earlier, this motion drags each sealing member panelacross the open end of the respective tubing segment, which exposes asurface of the panel or foil to the lumen within the respective fluidflow circuit. However, if heated sufficiently, such surfaces have beensterilized and because they are still hot when pulled from between thetubing segments, they remain sterile and do not contaminate or destroyany sterility of the fluid flow circuits. Also, because at least one(preferably both) of the resilient terminal end segments 82, 100 of eachof the fluid flow circuits is compressed when the housings areconnected, they (or at least one of them) simultaneously expand intodirect end-to-end contact with one another as the hot sealing membersare pulled from between them, and the molten end edges of the terminalsegments are progressively pressed together, without exposing theinterior of the fluid flow circuits to non-sterile ambient atmosphere,and immediately fuse or weld together to form a permanent junction orunion between the fluid flow circuits.

The connection apparatus and method described above have several safetyand reliability benefits in addition to those apparent from the abovedescription. Although the material of the end segments cools relativelyquickly, the surrounding housing 80, 98 protects the junction againstinadvertent user contact, touching or other interference with thesealing process. Also, each terminal end tubing segment 82, 100 isisolated from its respective tubing 78, 96 and the remainder of thefluid circuit by one of the rigid housings 80, 98. Thus, user movementor jostling of the tubing 78, 96 is isolated from the sterile junction.As noted earlier, the operation of the system can be visually confirmed,if desired, by viewing the location of the sealing members through theaccess port or slot 92.

The fluid circuit assembly is now ready for transfer of liquids betweenthe circuits or subassemblies, and if the fluid circuits werepre-sterilized, sterility has been maintained. No parts or pieces remainfor user disposal and no expensive wafer is required.

Another Alternative Embodiment

FIGS. 26 and 27 shows another embodiment that accommodates manualmovement of the sealing members. More specifically, FIG. 26 shows firstand second fluid flow circuits or subassemblies 120, 122 to be joined.The fluid flow circuits are preferably pre-sterilized and joined in amanner that preserves sterility. Fluid flow circuit 120 includes tubing124, rigid housing 126, heat meltable terminal tubing segment 128 andsealing member (panel) 130 sealing the end of the terminal tubingsegment. The housing 126 has an internal fluid flow path 132 with aninlet for attachment to tubing 124 and an outlet for attachment to theterminal tubing segment 128.

Similarly, fluid flow circuit 122 includes tubing 134, rigid housing136, heat meltable terminal tubing segment 138 and sealing member 140sealing the end of the terminal tubing segment. The housing 136 has aninternal fluid flow path 142 with an inlet for attachment to tubing 134and an outlet for attachment to the terminal tubing segment 138.

The housings 126, 136 are configured to be joined in preferablyirreversible attachment as shown in FIG. 27. In the configuration shownthere, the housings have complementary barbs and recesses that engagewhen the housings are pushed together and preferably preventdisconnection under ordinary usage conditions.

At least one of the sealing members 130, 140 includes a heating memberand, as preferred, the sealing members are identical thin multi-layerpanels having metallic foil on or near the distal surface and a materialsealingly attachable to the terminal tubing segment on the proximalsurface. The earlier discussion regarding sealing members appliesequally to this embodiment.

The housings 126, 136 are configured and dimensioned so that when thehousings are attached, the distal surfaces of the sealing members arebrought into direct face-to-face contact. At least one and preferablyboth of the terminal tubing segments are pliable and resilient, andcompressed by the housings when the housings are attached. The heatingelements of the sealing members are then heated, such as by inductiveheating or resistive heating, preferably until they reach sterilizingtemperature for sufficient time to effect sterilization of the surfacesof the sealing member (for example 260° C. or higher). This also resultsin heating of terminal tubing segments, raising at least the endportions of the segments above their melt temperature, to a moltenstate. At that time, the induction heating may be terminated and thesealing members are simultaneously gripped and pulled rapidly, whilestill hot, from between the tubing end segments. Because the portions ofthe sealing member panels that are pulled across the open end of thetubing segment are sterile and preferably still hot, they do not resultin contamination of either of the flow circuits. As the panels exit frombetween the tubing segments, the molten end edges of the tubing segmentsare forced simultaneously progressively together due to the compressioncaused by the housings, and the molten ends of the face-to-face tubingsegments fuse or weld to form a sterile permanent union or junctionbetween the circuits.

Antimicrobial Enhancement

In accordance with another aspect of this subject matter, thesterilizing/welding process time herein can be reduced in any of theabove apparatus, systems and methods employing sealing members that haveantimicrobial properties in whole or in pertinent part. Employingsealing members with surfaces having significant antimicrobialproperties can, in theory, reduce sterilization heating times by as muchas 50% or more as compared to other types of sealing members.

Antimicrobial surfaces potentially prevent or retard the growth ofbacteria, viruses and fungi. While various materials may haveantimicrobial properties, certain metals or metal alloys, includingconductive metals that are particularly useful in the present subjectmatter, have significant antimicrobial properties. These metals includesilver, copper, brass, stainless steel, titanium dioxide and alloysthereof, particularly silver and copper.

In the present subject matter, the sealing members may have all or aportion of its surface or heating element or member made of materialhaving antimicrobial properties—particularly that portion of the surfacethat is exposed to the inside of the attached fluid conduit. Thisportion of the surface is typically the surface that is exposed to theinside of the conduit while the sealing member is attached to theconduit and that is exposed to the inside of the conduit as the sealingmember is moved from between mating conduit ends during the sterilesealing process. Alternatively the entire proximal surface of eachsealing member (which is the surface that faces the conduit to which itis attached) or the entire proximal and distal surfaces of the sealingmembers could have antimicrobial properties.

In one implementation, a sealing member could be a single layer or foilof uncoated or bare metal having antimicrobial properties, such ascopper or copper alloy. Alternatively, the sealing member could, ifdesired, be a laminate with the requisite surfaces having antimicrobialproperties. For example, such a laminate could, if desired, include ametallic proximal surface and metallic distal surface with anintermediate layer of polymer adhesive or other material.

In one preferable aspect, the sealing member is a single layer of metalfoil or film, with bare and uncoated proximal and distal surfaces forfull antimicrobial effect. The flow conduit of a fluid circuit or fluidcircuit subassembly could be attached to the sealing member by applyinga suitable adhesive to the open end of the conduit and pressing thesealing member and conduit together until the adhesive cures. Thus, allthe surface of the sealing member exposed to the ambient atmosphere isbare exposed metal, such as copper, silver or other antimicrobialmaterial, that exhibits inherent antimicrobial properties forsubstantially preventing or retarding the growth of bacteria, virusesand/or fungi. Such properties may automatically provide a several logreduction of contamination load or bioburden on the sealing membersurfaces. The same may also be said of that portion of the sealingmember that is fully enclosed within the open end of the attachedconduit. That portion, however, is typically pre-sterilized with theinside of the attached fluid conduit and maintained sterile by the bondwith the open end of the conduit. The other portions of the sealingmember are exposed to potential contamination from the ambientatmosphere and the antimicrobial properties of significant benefit.

Sterilization in medical applications typically requires about a six logreduction in microbial burden. If the exposed surfaces of the sealingmember provide, by way of inherent antimicrobial effect, for example, athree log reduction, it is only necessary for the induction or otherheating that is used in the sterilizing/welding to provide the remainingthree log reduction to achieve satisfactory sterilization—significantlyreducing the amount of time required to achievesterilization—potentially by fifty percent (50%) or more, such assixty-six percent (66%). Such sealing members exhibiting increasedantimicrobial activity could be used with any of the assemblies,subassemblies, methods or apparatus described herein.

Although described in terms of preferred and alternative embodiments forpurposes of illustration, it is understood that other variations arewithin the scope of this disclosure. Such changes or variations mayinclude, without limitation, changes in shape, configuration, timing,materials, pressures and the like as would be apparent to a personskilled in the field upon reading this description.

The invention claimed is:
 1. A method of joining first and second fluidflow circuits to form a fluid flow circuit assembly, each fluid flowcircuit including a fluid flow conduit with a lumen and an open endterminating in a polymeric material and a sealing member attached to theflow conduit and sealing the open end thereof, and at least one of thesealing members including at least one single-use heating element as apre-assembled composite part of the sealing member prior to joining; (a)melting the polymeric material of the open ends by heating the at leastone heating element; (b) relatively separating the sealing members andthe respective open ends to which they are sealed to expose the openends; and (c) bringing the exposed open ends together while melted toform a junction between the fluid flow circuits that allows fluid flowtherebetween.
 2. The method of claim 1 wherein each of the sealingmembers comprises a panel attached to the open polymeric end of therespective conduit and at least one of the panels comprises a metalliclayer defining the heating element, the method including: positioningthe polymeric ends of the conduits generally in axial alignment and withthe respective panels in face to face contact, heating the metalliclayer sufficiently to melt the polymeric material of the open end ofeach conduit, separating the sealing members and the open ends bylaterally separating the panels from between the polymeric ends whilethe polymer is melted while applying an axial compressive force to theconduits so as to substantially simultaneously bring the open endstogether as the panels are separated from between the conduits; andcooling the molten ends while maintaining the axial compressive force toform a junction between the fluid conduits that allows fluid flowtherebetween.
 3. The method of claim 2 in which the conduits are heldgenerally laterally stationary during heating and the panels are movedlaterally from between the conduits.
 4. The method of claim 2 in whichthe metallic layer is electrically conductive and heated by an inductiveelectrical power source operating at a selected electrical frequency andthe metallic layer has a thickness not substantially greater than theskin depth for such metal at such frequency.
 5. The method of claim 2 inwhich the fluid flow circuits are pre-sterilized, and the panels and theopen ends are separated relative to one another and the melted ends arecompressed together while maintaining the sterility of the fluid flowcircuits.
 6. The method of claim of 2 in which the metallic layercomprises a material that exhibits an antimicrobial property.
 7. Themethod of claim 2 in which the metallic layer is heated to at leaststerilizing temperature for a time sufficient to sterilize the sealingmembers before moving the panels relative to the open ends.
 8. Themethod of claim 2 in which the polymeric material has a melt temperatureof about 230° C. or greater.
 9. The method of claim 2 in which each ofthe first and a second fluid flow circuits comprises a panel having aplurality of layers including a polymer layer and a metallic layerdefining the heating element.
 10. The method of claim 2 in which atleast one of the fluid flow circuits comprises a panel having aplurality of layers including two polymer layers and a metallic layerdefining the heating element located between the polymer layers.
 11. Themethod of claim 2 wherein the panel has a thickness of less than about0.5 mm.
 12. The method of claim 1 including sterilizing each of thefirst and second fluid flow circuit prior to steps (a)-(c).
 13. Themethod of claim 1 wherein the at least one heating element is heated toa sufficient temperature for a time sufficient to sterilize the sealingmembers.
 14. The method of claim 1 wherein the at least one heatingelement is heated to at least about 230° C.
 15. The method of claim 1wherein the at least one heating element is electrically conductive andis heated by induction.
 16. The method of claim 1 wherein at least oneof the sealing members comprises a metallic film defining the at leastone heating element.
 17. The method of claim 1 wherein at least one ofthe sealing members is heated by an inductive electrical power sourceoperating at an electrical frequency of “f” and the at least one memberincludes a metallic film having a thickness not substantially greaterthan the skin depth for such metal at such frequency.
 18. The method ofclaim 1 wherein at least the surface of the sealing member that isexposed to the interior of the fluid conduit comprises a material havingantimicrobial properties.
 19. The method of claim 1 wherein the fluidflow circuits are pre-sterilized and the sealing members and open endsare relatively separated and the melted ends are compressed togetherwhile maintaining sterility of the fluid flow circuits.
 20. The methodof claim 1 wherein the open end and sealing member of each fluid flowcircuit are carried by a housing configured for connection to thehousing of the other fluid flow circuit.
 21. The method of claim 1wherein each of the sealing members comprises a film including ametallic layer attached to the open polymeric end of the respectiveconduit, the method including: positioning the circuits with the openpolymeric ends of the conduits generally in alignment and with therespective films in face to face contact, heating the metallic layersufficiently to melt the polymeric material of the open end of eachconduit and sterilize the sealing members, separating the films from therespective open ends by laterally withdrawing the films substantiallysimultaneously from between the molten polymeric ends while pressing theopen ends of the conduits together; and cooling the open ends whilemaintaining the pressure, forming a junction between the fluid conduits.22. A method of joining first and second fluid flow conduits, eachhaving a lumen and an open end terminating in a polymeric material and asealing member attached to the flow conduit and sealing the open endthereof, and each of the sealing members including at least onesingle-use heating element as a pre-assembled composite part of thesealing member prior to joining, the method including: (a) placing thesealing members in face to face contact; (b) melting the polymericmaterial of the open ends by heating the at least one heating elementsof each sealing member; (c) separating the sealing members from therespective open ends by withdrawing the sealing members from between therespective open ends of the conduits while pressing the open ends of theconduits toward each other to bring the exposed open ends together whilemelted to form a junction between the fluid flow conduits that allowsfluid flow therebetween.
 23. The method of claim 22 wherein each of thesealing members comprises a panel attached to the open polymeric end ofthe respective conduit and each of the sealing members comprises a panelhaving a plurality of layers including a polymer layer and a metalliclayer defining the at least one heating element, the open polymeric endof the respective conduit being sealingly attached to the polymer layer,the method including: positioning the polymeric ends of the conduitsgenerally in axial alignment and with the respective panels in face toface contact, heating the metallic layers sufficiently to melt thepolymeric material of the open end of each conduit, laterally separatingthe panels from between the polymeric ends while the polymer is meltedto expose the open ends and while applying an axial compressive force tothe conduits so as to substantially simultaneously bring the exposedopen ends together as the panels are separated from between them; andcooling the melted ends while maintaining the axial compressive force toform a junction between the fluid conduits that allows fluid flowtherebetween.
 24. The method of claim 23 in which the heating element isheated by an inductive electrical power source operating at a selectedelectrical frequency and the heating element has a thickness notsubstantially greater than the skin depth for such metal at suchfrequency.
 25. The method of claim 22 in which the conduits arepre-sterilized, and the melted ends are joined while maintaining thesterility of the conduits.
 26. The method of claim of 22 in which thesealing member comprises a material that exhibits an antimicrobialproperty.
 27. The method of claim 22 in which the heating element isheated to at least sterilizing temperature for a time sufficient tosterilize the sealing members before separating them relative to theopen ends.
 28. The method of claim 22 wherein each sealing memberincludes a panel having a thickness of less than about 0.5 mm.